Quality of life after cytoreductive surgery and HIPEC: A single centre prospective study.

PURPOSE: Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has become a crucial method in the management of peritoneal metastasis. This study evaluated the Quality of Life (QoL) post CRS plus HIPEC. METHODS: 80/95 patients underwent CRS plus HIPEC at the Metaxa Cancer Hospital, Piraeus, Greece from 06/2011 to 06/2015 and completed the colorectal version of the Functional Assessment of Cancer Therapy questionnaire (FACTC, version 4) at 1 week pre-operatively and at 1, 3, 6, 12, 18, 24 months post-operatively. The subscales assessed were the physical, social/family, emotional and functional wellbeing. RESULTS: In all subscales, fluctuations in the scores indicated a worsening of QoL in the first 3 post-operative months, followed by improvement back to pre-operative levels and even better scores later on. Statistical improvement was proven for the physical and emotional well-being subscales. CONCLUSIONS: The significant improvement in the physical well-being is attributed to the eradication of symptoms, whereas the relevant improvements in the emotional wellbeing subscale are explained both by the pre-operative desperation of the diagnosis or relapse of malignancy, and the post-operative hopefulness after a successful operation.

Survival and nutritional factors on home parenteral nutrition (HPN): Our initial experience.

PURPOSE: Home parenteral nutrition (HPN) has been proposed as the treatment of choice in patients suffering from intestinal failure (IF) and has been claimed to improve survival and quality of life either in patients with benign disorders or even in those with malignancies. The purpose of the present analysis was to report characteristics and outcomes of adult patients with IF receiving HPN in Greece. METHODS: Patients that received HPN between 2011 and 2017 were included in this retrospective analysis. Characteristics of the included patients, cause of HPN, duration of HPN, route of HPN administration, complications as well as survival rates were recorded. RESULTS: A total of 189 patients were included in the present analysis. Of these, 163 (86.3%) suffered from cancer while 26 (13.7%) received HPN due to non-malignant diseases. The reported mortality was 74.6% while overall severe complications rate was 77%. CONCLUSIONS: According to the findings of our study, HPN seems to have beneficial effect but it should be considered with caution by the physicians who should take into account the indications of each patient to receive parenteral nutrition, the underlying disease and prognosis and the access of each patient to home care services.

Post-translational processing of beta-secretase in Alzheimer's disease.

Beta-amyloid is released into the brains of Alzheimer's patients, where it aggregates and causes damage to neurons. It is cleaved proteolytically from a large transmembrane glycoprotein amyloid precursor protein by a membrane-bound protease, known as beta-secretase identified previously as the acid protease, Asp-2. We have shown previously that beta-secretase is up-regulated by increased intracellular cholesterol, and down-regulated by cholesterol biosynthesis inhibition. Here we show using mass spectrometry that discrete changes in the glycosylation and palmitoylation of beta-secretase occur when cells expressing it are treated with statins.

The regulation of beta-secretase by cholesterol and statins in Alzheimer's disease.

Epidemiologists have found a decreased risk of developing Alzheimer's disease (AD) in people taking statins (cholesterol biosynthesis inhibitors). We have reported previously that, in cell culture, lovastatin decreases the output of beta-amyloid, a peptide that is toxic to neurones, and is reputably the prime cause of neurodegeneration seen in AD. This report probes the mechanism of statin protection further by finding out how the protease beta-secretase, that releases beta-amyloid from its precursor protein, behaves under changed cholesterol levels induced by statins. We found that, with high cellular cholesterol levels, there is a decrease in glycosylation of mature oligosaccharides in beta-secretase, whereas in the presence of lovastatin, glycosylation progresses further. Moreover, lovastatin does not inhibit beta-secretase in vitro. Thus, the cholesterol and statin effects are due to changes in cellular targeting induced by changed cholesterol gradients. Some of these changes are mimicked by the action of U18666A, a cholesterol-transport inhibitor that produces a defect in cells seen in patients with Neimann Pick's disorder.

Pro-domain removal in ASP-2 and the cleavage of the amyloid precursor are influenced by pH.

BACKGROUND: One of the signatures of Alzheimer's disease is the accumulation of aggregated amyloid protein, Abeta, in the brain. Abeta arises from cleavage of the Amyloid Precursor protein by beta and gamma secretases, which present attractive candidates for therapeutic targeting. Two beta-secretase candidates, ASP-1 and ASP-2, were identified as aspartic proteases, both of which cleave the amyloid precursor at the beta-site. These are produced as immature transmembrane proteins containing a pro-segment. RESULTS: ASP-2 expressed in HEK293-cells cleaved the Swedish mutant amyloid precursor at different beta-sites at different pHs in vitro. Recent reports show that furin cleaves the pro-peptide of ASP-2, whereas ASP-1 undergoes auto-catalysis. We show that purified recombinant ASP-2 cleaves its own pro-peptide at ph 5 but not pH 8.5 as seen by mass spectrometry, electrophoresis and N-terminal sequencing. CONCLUSION: We suggest that ASP-2 processing as well as activity are influenced by pH, and hence the cellular localisation of the protein may have profound effects on the production of Abeta. These factors should be taken into consideration in the design of potential inhibitors for these enzymes.